This research proposal continues our studies on the mechanism of action of antigen in inducing the immune response and on the genetic control of the immune response in the inbred rat. We showed that the antibody response to poly (Glu52Lys33Tyr15) is linked to the major histocompatibility locus, and current studies indicate that the binding constant and specificity of the antibody are also linked. We will next explore the relationship of the mixed lymphocyte reactivity locus and PHA-responsiveness locus to the immune response. Studies on the genetic characterization of inbred rats and the development of congenic lines will continue, and they will provide support for the studies on the genetic control of the immune response. Our investigation of the cellular basis of the genetic control will focus on the immunoglobulin classes in which control is exerted, the kinetics of the cellular response and the mechanism by which antigen aggregation alters the response. Finally, we will study the genetic control of the delayed hypersensitivity response using the production of soluble mediators, particularly MIF, and skin testing as the assay systems. These studies should allow us to construct a linkage map in the rat for the Ag-B, IR(GLT), MLR, PHA and DH(GLT) loci. BIBLIOGRAPHIC REFERENCES: Poloskey, P. E., Kunz, H. W., Gill, T. J. III, Shonnard, J. W., Hansen, C. T., and Dixon, B. D., Genetic studies in inbred rats. IV. Xenoantisera against rat erythrocyte (Ag-C) antigens. J. Immunogenetics 2, 179 (1975). Poloskey, P. E., Kunz, H. W., and Gill, T. J. III, Genetic studies in inbred rats. V. Xenoantisera against two major histocompatibility antigens raised by immunization with red cells. J. Immunogenetics 2, 189 (1975).